NUCB2, also known as nucleobindin 2, is a member of the nucleobindin family. Its encoded peptide NUCB2/nesfatin-1 has been implicated in multiple physiological functions. It plays a vital role in diet and energy homeostasis, and is involved in regulating processes such as food intake, body weight, and glucose and fat metabolism [1,2,4,6]. It may also participate in various signal-pathways related to tumorigenesis [1]. Genetic models, like KO/CKO mouse models, can be valuable for studying its functions in vivo.

In osteosarcoma, depletion of NUCB2 in in vitro and in vivo models reduced cell proliferation and metastatic potential. It was found that NUCB2 ablation suppressed CXCL8 expression, reduced PD-L1 expression, and stimulated anti-tumor immunity mediated by cytotoxic T cells. Moreover, NUCB2 interacted with NUCKS1 to inhibit its degradation, which was responsible for the transcriptional regulation of CXCL8 expression [3]. In breast cancer cells, higher NUCB2 expression was associated with less malignant tumors, ER-positive and PR-positive phenotypes, and longer patient survival, suggesting its role in malignant transformation and as a positive prognostic factor [5].

In conclusion, NUCB2 is crucial for regulating energy-related physiological functions. Model-based research, especially in KO/CKO mouse models, has revealed its significance in cancer-related processes such as tumor progression and immune regulation in osteosarcoma and breast cancer, providing insights into potential therapeutic targets.